Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation
Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation
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DOI：
10.1053/meta.2000.17695
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发表时间：
2000-11-01
影响因子：
9.8
通讯作者：
Millard, WJ
中科院分区：
文献类型：
--
作者：
Martin, RL;Perez, E;Millard, WJ
众所周知，瘦素在体重调节中起主导作用。瘦素受体在下丘脑中尤其丰富，那里是瘦素的大部分生物活性发生的地方。在瘦素没有或活性有限的情况下，很容易牵涉到瘦素抵抗，并推测可能发生抵抗的多重狂欢。我们假设瘦素抵抗与下丘脑瘦素受体下调有关。将大鼠随机分为3组，分别给予磷酸盐缓冲盐水(PBS)或低剂量或高剂量瘦素，持续给药28天。每天测量体重和食物摄入量。在研究期间，长期的瘦素治疗导致体重呈剂量依赖性的下降。它导致了剂量依赖的食物摄入量的减少，但只在研究的前半部分。在第3周进行瘦素抵抗测试，显示两个治疗组对瘦素厌食作用的抵抗发展。抵抗力测试的结果以及食物摄入量数据表明，在研究的最后两周，对瘦素调节食欲的效果产生了抵抗性。此外，我们还发现下丘脑Leptin受体mRNA和蛋白表达下调，这可能是Leptin摄食效应丧失的机制之一。版权所有(C)2000，由W.B.Saunders公司提供。
It is well known that leptin plays a predominant role in body weight regulation. Leptin receptors are especially abundant in the hypothalamus, where the majority of leptin's biologic activity occurs. In instances where leptin has no or limited activity, it is easy to implicate leptin resistance and speculate as to the multiple revels where resistance may occur. We hypothesize that leptin resistance is associated with hypothalamic leptin receptor downregulation. Rats were randomly divided into 3 groups receiving phosphate-buffered saline (PBS) or low- or high-dose leptin continually over a 28-day period. Body weight and food intake were measured daily. Long-term leptin treatment resulted in a dose-dependent decrease in body weight for the duration of the study. It a Iso resulted in a dose-dependent decrease in food intake, but only for the first half of the study. A test of leptin resistance was performed at week 3 demonstrating the development of resistance to the anorectic effects of leptin in both treatment groups. The results of the resistance test together with the food intake data suggest that resistance to the appetite-regulating effects of leptin developed during the final 2 weeks of the study. In addition, we show a down-regulation of leptin receptor mRNA and protein in the hypothalamus, which may be one of the mechanisms by which the food-intake effects of leptin were lost. Copyright (C) 2000 by W.B. Saunders Company.